The objective of this proposal is an investigation of platelet function as an in vitro model of non-immunologic pharmacodynamic factors which regulate bronchomotor tone in human asthma. Previous experiments in this laboratory have demonstrated abnormal patterns of epinephrine- induced platelet aggregation in many asthmatic patients and further elaboration of these studies is considered to be worthwhile. In the present investigation, a platelet aggregation profile (ADP, epinephrine, collagen and thrombin) will be determined in immunologic and non- immunologic asthma. The individual variability of these reactions as well as possible differences between symptomatic and asymptomatic clinical states will also be studied. These results will be analyzed to ascertain the value of platelet aggregation as a differential diagnostic test between the major types of asthma. Platelet membrane receptors which mediate aggregation by ADP, epinephrine, collagen and thrombin in asthma will also be studied. In the course of these experiments, factors such as cyclic AMP, platelet factors 3 and 4, metabolically inactive ADP and serotonin, which are released during the platelet aggregation phenomenon, will also be assayed. Special studies will also be performed in aspirin-intolerant patients and the effect of various bronchial challenge experiments upon platelet aggregation will also be determined. A more intensive study of plasma or humoral factors, which were previously demonstrated to cause abnormal aggregation of normal platelets, will be assessed as a means of ascertaining genetic predisposition or susceptibility in certain types of asthma.